(E)-2-Cyano-3-(substituted phenyl)acrylamide analogs as potent inhibitors of tyrosinase: A linear β-phenyl-α,β-unsaturated carbonyl scaffold.

Abstract

In this study, we synthesized (E)-2-cyano-3-(substituted phenyl)acrylamide (CPA) derivatives which possess a linear β-phenyl-α,β-unsaturated carbonyl scaffold and examined their inhibitory activities against tyrosinase. CPA analogs exerted inhibitory activity against mushroom tyrosinase. Results from the docking simulation indicated that CPA2 could bind directly to the active site of mushroom tyrosinase and the binding affinity of CPA2 for tyrosinase might be higher than that of kojic acid, a well-known potent tyrosinase inhibitor. In B16F10 cells, CPA2 significantly suppressed tyrosinase activity and melanogenesis in a dose-dependent manner. At the concentration of 25μM, CPA2 exhibited tyrosinase inhibitory activity comparable to that of kojic acid with no cytotoxic effect. Results from the present study suggest that CPA2 bearing a linear β-phenyl-α,β-unsaturated carbonyl scaffold may be the potential candidate for treatment of diseases associated with hyperpigmentation and that a linear β-phenyl-α,β-unsaturated carbonyl scaffold might be closely related to potent tyrosinase inhibition.

• Authors: Sujin Son, Haewon Kim, Hwi Young Yun, Do Hyun Kim, Sultan Ullah, Seong Jin Kim, Yeon-Jeong Kim, Min-Soo Kim, Jin-Wook Yoo, Pusoon Chun, Hyung Ryong Moon
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 23 Issue 24 Pg. 7728-34 (12 15 2015) ISSN: 1464-3391 [Electronic] England
• PMID: 26631438 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Enzyme Inhibitors
• Melanins
• Acrylamide
• Monophenol Monooxygenase

Topics

• Acrylamide (chemistry, pharmacology)
• Agaricales (enzymology)
• Animals
• Cell Line, Tumor
• Enzyme Inhibitors (chemistry, pharmacology)
• Melanins (metabolism)
• Mice
• Molecular Docking Simulation
• Monophenol Monooxygenase (antagonists & inhibitors, metabolism)